02/13/2025 David Secord, DPM
Fall Risk Assessment When Choosing Between Gabapentin and Duloxetine z9Paul Kesselman, DPM)
There are different classes of medications used to
treat peripheral neuropathy, including SSRI’s,
Tri-cyclics, SSRNI’s, anti-convulsants and anti-
depressants. My experience is with Gabapentin,
Pregabalin, Duloxetine, Doxepin and Amitriptyline.
The goal in dosing these (besides drug/drug
interaction concerns) is a balance between
effectiveness and anticholinergic side-effects
while also looking at potential onset of
extrapyramidal syndrome. The medication which has
a flag for extrapyramidal symptoms is
Amitriptyline and I always avoid its usage in
anyone with peripheral neuropathy who is over the
age of 60 and may have a drug/drug interaction
exacerbating this.
I’ve found that amitriptyline is very effective
and inexpensive, but can have the most pronounced
anticholinergic side-effects. My go to med for
peripheral neuropathy is Duloxetine, as it appears
to have the least anticholinergic side-effects and
the least incidence of extrapyramidal symptoms. In
my experience, Gabapentin appears to be the least
effective, with nearly the same level of
anticholinergic side-effects and extrapyramidal
symptoms as Pregabalin (which I also don’t think
is very effective) and Doxepin.
Of the different causes of peripheral neuropathy,
I’ve found that these medications appear to work
well with Diabetic peripheral neuropathy. For the
other causes of peripheral neuropathy:
• Autoimmune diseases. These include Sjogren's
syndrome, lupus, rheumatoid arthritis, Guillain-
Barre syndrome, chronic inflammatory demyelinating
polyneuropathy and vasculitis. Also, some cancers
related to the body's immune system can cause
polyneuropathy. These are a form of autoimmune
disorder called paraneoplastic syndrome.
• Idiopathic. This is the second most common and
has no identifiable cause.
• Infections. These include certain viral or
bacterial infections, including Lyme disease,
shingles, hepatitis B and C, leprosy, diphtheria,
and HIV.
• Inherited disorders. Disorders such as Charcot-
Marie-Tooth disease are hereditary types of
neuropathy that run in families.
• Tumors. Cancerous growths, also called
malignant, and noncancerous growths, also called
benign, can grow on or press on nerves.
• Bone marrow disorders. These include a protein
in the blood that isn't usually there, called
monoclonal gammopathies, a rare form of myeloma
that affects the bones, lymphoma and the rare
disease amyloidosis.
• Other diseases. These include metabolic
conditions such as kidney disease or liver
disease, and an underactive thyroid, also known as
hypothyroidism.
• Alcoholism. Unhealthy dietary choices made by
people with alcohol use disorder, also known as
alcoholism, and poor absorption of vitamins can
lead to low amounts of essential vitamins in the
body.
• Exposure to poisons. Toxic substances include
industrial chemicals and heavy metals such as lead
and mercury.
• Medicines. Certain medicines, especially
chemotherapy used to treat cancer, can cause
peripheral neuropathy. (I’ve found that Cisplatin-
induced peripheral neuropathy is especially
common.)
• Injury or pressure on the nerve. Injuries, such
as from motor vehicle accidents, falls or sports
injuries, can sever or damage peripheral nerves.
Nerve pressure can result from having a cast or
using crutches or repeating a motion such as
typing many times.
• Low vitamin levels. B vitamins, including B-1,
B-6 and B-12, as well as copper and vitamin E are
crucial to nerve health.
They are less effective. In those with peripheral
neuropathy from heavy-metal exposure, I haven’t
found a medication which appears to be effective.
In summation, my clinical experience has been the
diametric opposite of the conclusion of the
published study, in that Duloxetine was the most
effective and had the least extrapyramidal
symptoms (and the least anticholinergic side-
effects of dry eyes, dry mouth, constipation and
dizziness) and Gabapentin was the least effective
and had the most pronounced extrapyramidal
symptoms (and the more pronounced anticholinergic
side-effects.)
David Secord, DPM, McAllen, TX
